Maternal Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccination During Pregnancy: Impact on Infant Anti-Pertussis Antibody Concentrations by Maternal Pertussis Priming Series.

BACKGROUND: Acellular pertussis (aP) vaccines replaced whole-cell pertussis (wP) vaccines for the US childhood primary series in 1997. As women primed with aP vaccines enter childbearing age, protection of infants through tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination during pregnancy may be impacted. METHODS: Term infants born to women vaccinated with Tdap during pregnancy were included. Geometric mean concentrations (GMCs) of pertussis-specific immunoglobulin G antibodies (international units per milliliter) in cord blood of infants born to women born after 1997 (aP-primed) were compared with those born to women born before 1992 (wP-primed). RESULTS: 253 and 506 infants born to aP- and wP-primed women, respectively, were included. Compared with wP-primed women, aP-primed women were younger, more likely to be Hispanic or non-Hispanic Black, and had lower-birthweight infants (P < .01 for all). Antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) were lower among infants born to aP-primed vs wP-primed women (PT, 17.3 vs 36.4; GMC ratio, .475; 95% confidence interval [CI], .408-.552 and FHA, 104.6 vs 121.4; GMC ratio, 0.861; 95% CI, .776-.958). No differences were observed for anti-fimbriae or anti-pertactin antibodies. CONCLUSIONS: Transplacental anti-pertussis antibody concentrations in infants of women vaccinated with Tdap during pregnancy differed by type of childhood vaccine the women received. Notably, anti-PT antibody levels, considered most important in preventing severe infant disease, were lower in infants born to aP-primed vs wP-primed women. Maternal Tdap vaccination may confer less protection against pertussis in infants born to aP-primed vs those born to wP-primed women.

Association Between Third-Trimester Tdap Immunization and Neonatal Pertussis Antibody Concentration.

Importance: Immunization with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in the United States during weeks 27 through 36 of pregnancy to prevent life-threatening infant pertussis. The optimal gestation for immunization to maximize concentrations of neonatal pertussis toxin antibodies is unknown. Objective: To determine pertussis toxin antibody concentrations in cord blood from neonates born to women immunized and unimmunized with Tdap vaccine in pregnancy and optimal gestational age for immunization to maximize concentrations of neonatal antibodies. Design, Setting, and Participants: Prospective, observational, cohort study of term neonates in Houston, Texas (December 2013-March 2014). Exposures: Tdap immunization during weeks 27 through 36 of pregnancy or no Tdap immunization. Main Outcomes and Measures: Primary outcome was geometric mean concentrations (GMCs) of pertussis toxin antibodies in cord blood of Tdap-exposed and Tdap-unexposed neonates and proportions of Tdap-exposed and Tdap-unexposed neonates with pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher, cutoffs representing quantifiable antibodies or levels that may be protective until the infant immunization series begins. Secondary outcome was the optimal gestation for immunization to achieve maximum pertussis toxin antibodies. Results: Six hundred twenty-six pregnancies (mean maternal age, 29.7 years; 41% white, 27% Hispanic, 26% black, 5% Asian, 1% other; mean gestation, 39.4 weeks) were included. Three hundred twelve women received Tdap vaccine at a mean gestation of 31.2 weeks (range, 27.3-36.4); 314 were unimmunized. GMC of neonatal cord pertussis toxin antibodies from the Tdap-exposed group was 47.3 IU/mL (95% CI, 42.1-53.2) compared with 12.9 IU/mL (95% CI, 11.7-14.3) in the Tdap-unexposed group, for a GMC ratio of 3.6 (95% CI, 3.1-4.2; P < .001). More Tdap-exposed than Tdap-unexposed neonates had pertussis toxin antibody concentrations of 15 IU/mL or higher (86% vs 37%; difference, 49% [95% CI, 42%-55%]), 30 IU/mL or higher (72% vs 17%; difference, 55% [95% CI, 49%-61%]), and 40 IU/mL or higher (59% vs 12%; difference, 47% [95% CI, 41%-54%]); P < .001 for each analysis. GMCs of pertussis toxin antibodies were highest when Tdap vaccine was administered during weeks 27 through 30 and declined thereafter, reaching a peak at week 30 (57.3 IU/mL [95% CI, 44.0-74.6]). Conclusions and Relevance: Immunization with Tdap vaccine during the third trimester of pregnancy, compared with no immunization, was associated with higher neonatal concentrations of pertussis toxin antibodies. Immunization early in the third trimester was associated with the highest concentrations.

Rotavirus Strain Trends During the Postlicensure Vaccine Era: United States, 2008-2013.

BACKGROUND: Group A rotaviruses (RVA) are a significant cause of pediatric gastroenteritis worldwide. The New Vaccine Surveillance Network (NVSN) has conducted active surveillance for RVA at pediatric hospitals and emergency departments at 3-7 geographically diverse sites in the United States since 2006. METHODS: Over 6 consecutive years, from 2008 to 2013, 1523 samples from NVSN sites that were tested positive by a Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention for genotyping. RESULTS: In the 2009, 2010, and 2011 seasons, genotype G3P[8] was the predominant genotype throughout the network, with a 46%-84% prevalence. In the 2012 season, G12P[8] replaced G3P[8] as the most common genotype, with a 70% prevalence, and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq; Rotarix) strains were detected in 0.6%-3.4% of genotyped samples each season. Uncommon and unusual strains (eg, G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], and G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype. CONCLUSIONS: Continued active surveillance is needed to monitor RVA genotypes in the United States and to detect potential changes since vaccine licensure.

Immune Responses to Invasive Group B Streptococcal Disease in Adults.

Immunization of nonpregnant adults could help prevent invasive group B Streptococcus (GBS) infections, but adult immune responses have not been investigated. We defined capsular polysaccharide (CPS) and pilus island (PI) surface antigen distribution and expression and immune responses to GBS infection in nonpregnant adults. Prospective surveillance from 7 hospitals in Houston, Texas, USA, identified 102 adults with GBS bacteremia; 43% had skin/soft tissue infection, 16% bacteremia without focus, and 12% osteomyelitis. CPS-specific IgG was determined by ELISA and pilus-specific IgG by multiplex immunoassay. CPS types were Ia (24.5%), Ib (12.7%), II (9.8%), III (16.7%), IV (13.7%), and V (12.7%); 9.8% were nontypeable by serologic methods. Pili, expressed by 89%, were most often PI-2a. CPS and pilus-specific IgG increased during convalescence among patients with strains expressing CPS or PI. All GBS expressed CPS or PI; 79% expressed both. Increased antibodies to CPS and PI during recovery suggests that GBS bacteremia in adults is potentially vaccine preventable.

Maternal antibody at delivery protects neonates from early onset group B streptococcal disease.

BACKGROUND: Further reduction in the group B streptococcal (GBS) disease burden in neonates in the United States awaits an additional prevention strategy, such as maternal immunization. METHODS: We performed a prospective, multicenter, case-control study of 33 mothers delivering neonates with early onset GBS infection (cases), and 99 age- and ethnicity-matched mothers colonized with the same capsular polysaccharide (CPS) types delivering healthy neonates (controls). Relative risk and absolute risk were calculated for early onset disease associated with concentrations of type Ia, III, or V CPS-specific antibody in maternal serum. RESULTS: For GBS types Ia and III, maternal CPS-specific antibody concentrations of ≥ 0.5 µg/mL were associated with a relative risk of approximately 0.1 (95% confidence intervals [CIs], .01-.74 and 0-.72, respectively; P = .02 for each), corresponding to a 90% risk reduction (by logistic regression). For type V, the relative risk was 0.3 (95% CI, .01-3.1), corresponding to a 70% risk reduction. By Bayesian modeling, the risk of early onset disease would decrease by 70% if maternal CPS-specific antibody concentrations for these 3 GBS types were ≥ 1 µg/mL. CONCLUSIONS: Maternal CPS-specific antibody serum concentrations of ≥ 1 µg/mL at the time of delivery appear to protect most neonates from early onset GBS type Ia and III disease.

Importance of timing of maternal combined tetanus, diphtheria, and acellular pertussis (Tdap) immunization and protection of young infants.

BACKGROUND: Pertussis booster vaccine (Tdap) recommendations assume that pertussis-specific antibodies in women immunized preconception, during, or after previous pregnancies persist at sufficient levels to protect newborn infants. METHODS: Pertussis-specific immunoglobulin G (IgG) was measured by IgG-specific enzyme-linked immunosorbent assay (ELISA) in maternal-umbilical cord serum pairs where mothers received Tdap during the prior 2 years. Geometric mean concentrations (GMCs) of pertussis antibodies and cord-maternal GMC ratios were calculated. RESULTS: One hundred five mothers (mean age, 25.3 years [range, 15.3-38.4 years]; mean gestation, 39 weeks [range, 37-43 weeks]) immunized with Tdap vaccine a mean of 13.7 months (range, 2.3-23.9 months) previously were included; 72 (69%) had received Tdap postpartum, 31 at a routine healthcare visit and 2 as contacts of another newborn. There was no difference in GMCs for pertussis-specific IgG in maternal delivery or infant cord sera for women immunized before (n = 86) or during (n = 19) early pregnancy. Placental transport of antibodies was 121%-186% from mothers immunized before and during pregnancy, respectively. Estimated GMC of IgG to pertussis toxin was <5 ELISA units (EU)/mL at infant age 2 months (start of infant immunization series). More infants of mothers immunized during pregnancy had pertussis toxin levels estimated to be higher than the lower limit of quantitation of the assay (4 EU/mL) through age 2 months (52% vs 38%; P = .34). CONCLUSIONS: Infants of mothers immunized preconception or in early pregnancy have insufficient pertussis-specific antibodies to protect against infection. Maternal immunization during the third trimester, immunization of other infant contacts, and reimmunization during subsequent pregnancies may be necessary.

Effectiveness of pentavalent and monovalent rotavirus vaccines in concurrent use among US children <5 years of age, 2009-2011.

BACKGROUND: We assessed vaccine effectiveness (VE) for RotaTeq (RV5; 3 doses) and Rotarix (RV1; 2 doses) at reducing rotavirus acute gastroenteritis (AGE) inpatient and emergency department (ED) visits in US children. METHODS: We enrolled children <5 years of age hospitalized or visiting the ED with AGE symptoms from November 2009-June 2010 and from November 2010-June 2011 at 7 medical institutions. Fecal specimens were tested for rotavirus by enzyme immunoassay and genotyped. Vaccination among laboratory-confirmed rotavirus cases was compared with rotavirus-negative AGE controls. Regression models calculated VE estimates for each vaccine, age, ethnicity, genotype, and clinical setting. RESULTS: RV5-specific analyses included 359 rotavirus cases and 1811 rotavirus-negative AGE controls. RV1-specific analyses included 60 rotavirus cases and 155 rotavirus-negative AGE controls. RV5 and RV1 were 84% (95% confidence interval [CI], 78%-88%) and 70% (95% CI, 39%-86%) effective, respectively, against rotavirus-associated ED visits and hospitalizations combined. By clinical setting, RV5 VE against ED and inpatient rotavirus-associated visits was 81% (95% CI, 70%-84%) and 86% (95% CI, 74%-91%), respectively. RV1 was 78% (95% CI, 46%-91%) effective against ED rotavirus disease; study power was insufficient to evaluate inpatient RV1 VE. No waning of immunity was evident during the first 4 years of life for RV5, nor during the first 2 years of life for RV1. RV5 provided genotype-specific protection against each of the predominant strains (G1P[8], G2P[4], G3P[8], G12P[8]), while RV1 VE was statistically significant for the most common genotype, G3P[8]. CONCLUSIONS: Both RV5 and RV1 significantly protected against medically attended rotavirus gastroenteritis in this real-world assessment.

Symptomatic infection and detection of vaccine and vaccine-reassortant rotavirus strains in 5 children: a case series.

Vaccine or vaccine-reassortant rotavirus strains were detected in fecal specimens from 5 of 106 (4.7%) immunocompetent children who required treatment for rotavirus gastroenteritis at a large pediatric hospital in Texas in 2009-2010. Four strains were related to pentavalent rotavirus vaccine, whereas one was related to monovalent rotavirus vaccine. The contribution of these strains to each patient's illness was unclear given that 2 patients had prominent respiratory symptoms and 2 were concurrently infected with another pathogen (group F adenovirus and norovirus). Continued monitoring is necessary to assess the role of vaccine strains and vaccine-reassortant strains in pediatric rotavirus infections.

Impact of maternal postpartum tetanus and diphtheria toxoids and acellular pertussis immunization on infant pertussis infection.

BACKGROUND: Mothers often are the source of pertussis illness in young infants. The Centers for Disease Control and Prevention recommend tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine for postpartum women before hospital discharge. In January 2008, this recommendation was implemented in a predominantly Hispanic, medically underserved population at Ben Taub General Hospital (BTGH) in Houston (hereafter the intervention population). METHODS: A cross-sectional study compared preintervention (July 2000 through December 2007) and postintervention (January 2008 through May 2009) periods. Pertussis diagnosis was determined using International Classification of Diseases, Ninth Revision (ICD-9) codes and microbiology reports from 4 major children's hospitals in Houston. Only those infants ≤6 months of age with laboratory-confirmed pertussis illness were included. The proportions of pertussis-infected infants born at BTGH in the pre- and postintervention periods were compared. RESULTS: Of 514 infants with pertussis, 378 (73.5%) were identified during preintervention and 136 (26.5%) during postintervention years. These groups were similar in age (mean, 79.3 vs 72 days; P = .08), sex (males, 55% vs 52%; P = .48), length of hospitalization (mean, 9.7 vs 10.7 days; P = .62), mortality (2 deaths each; P = .29) and hospital of pertussis diagnosis. After adjustment for age, sex, and ethnicity, the proportions of pertussis-infected infants born at BTGH and potentially protected through maternal postpartum Tdap immunization were similar for the 2 periods (6.9% vs 8.8%; odds ratio, 1.06; 95% confidence interval, 0.5-2.2; P = .87). CONCLUSIONS: Immunizing only postpartum mothers with Tdap vaccine did not reduce pertussis illness in infants ≤6 months of age. Efforts should be directed at immunizing all household and key contacts of newborns with Tdap, not just mothers.

Invasive Group B Streptococcal Disease In Childhood.

Invasive group B streptococcal disease in childhood is uncommon and occupies a unique clinical niche. We present 10 children, 1-17 years of age, with invasive group B streptococcal disease from 2010 to 2020. Seven had conditions predisposing to infection and 3 had no identifiable risk factors. With appropriate consideration of pathogenesis, source control, and treatment, all children recovered.

Group B Streptococcal Cellulitis-Adenitis Syndrome in Infants: Insights From 24 Years of Experience.

This series of 28 infants with group B streptococcal (GBS) cellulitis-adenitis from a single institution over 24 years offers insights important to the early recognition, spectrum of findings, and optimal management of this rare manifestation of invasive GBS disease.

Implementation of cocooning against pertussis in a high-risk population.

BACKGROUND: In 2006, the Advisory Committee on Immunization Practices recommended tetanus, diphtheria, acellular pertussis (Tdap) vaccination of all caregivers of infants aged <1 year ("cocooning") to prevent pertussis-related complications and deaths. We implemented cocooning in a predominantly Hispanic, medically underserved, uninsured population at a Houston hospital. Phase 1 (January 2008-January 2010) provided maternal postpartum Tdap vaccine; Phase 2 (June 2009-January 2010) also vaccinated infant contacts on-site. METHODS: Pertussis education was provided to health care personnel and mothers. Standing orders for maternal postpartum Tdap vaccination were initiated. Mothers were interviewed to ascertain the number of additional infant contacts eligible to receive Tdap vaccine. Consenting eligible contacts received Tdap vaccine as soon as possible after delivery. RESULTS: From 7 January 2008 through 31 January 2010, 8334 (75%) of 11,174 postpartum women received Tdap vaccine. During Phase 2, 2969 (86%) of 3455 postpartum women were vaccinated; another 197 (6%) had previously received Tdap vaccine. Mothers were Hispanic (91.4%), black (5.4%), white (0.8%), Asian (1.4%) and other (1.0%). A median of 3 (range, 1-11) other Tdap-eligible contacts per infant were identified, and a median of 2 (range, 0-10) contacts per infant received Tdap vaccine. Of 1860 contacts vaccinated, 1813 (98%) anticipated daily infant contact. A total of 1697 (91%) received Tdap vaccine before infant hospital discharge, and 144 (8%) received Tdap vaccine within 7 days after hospital discharge. Barriers to full cocooning included the need for extended vaccination hours, visiting restrictions because of pandemic H1N1 influenza, and inaccurate recall of vaccination history. CONCLUSION: Although practical and logistical barriers exist, Tdap cocooning was well accepted by and successfully implemented in a high-risk population by using standing orders and providing vaccinations on-site.

Kinetics of maternal pertussis-specific antibodies in infants of mothers vaccinated with tetanus, diphtheria and acellular pertussis (Tdap) during pregnancy.

BACKGROUND: Kinetics of Tdap-induced maternally-derived antibodies in infants are poorly understood. Pre-Tdap era data suggest that maternal pertussis antibodies in infants have a half-life of approximately 5-6 weeks. METHODS: 34 mother-infant pairs had blood collected before maternal Tdap vaccination, 4 weeks later, at delivery (maternal and cord), and at infant ages 3 and 6 weeks from June 2014-March 2015. Immunoglobulin G (IgG) to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbrial proteins (FIM) and pertactin (PRN) was quantified by multiplex luminex assay (IU/ml). Geometric mean concentrations (GMCs) with 95% confidence intervals (C.I.) and half-life of pertussis antibodies were calculated. RESULTS: Tdap was administered to 34 women (mean age 31.1 years) at mean gestation 30.7 weeks (28-32.7). Mean neonatal gestation was 39.1 weeks (36-41.1) and mean birthweight was 3379 g (2580-4584). Four weeks post-Tdap vaccination, maternal pertussis-specific IgG GMCs increased ≥4-fold in 59%, 41%, 29% and 44% of women for PT, FHA, FIM and PRN, respectively, and then waned. The transplacental transport ratio of pertussis antibodies was 1.35 for PT, 1.41 for FHA, 1.31 for FIM and 1.36 for PRN. Between birth and age 6 weeks, infant serum GMC for PT-specific IgG decreased from 55.1 IU/mL (38.6-78.6) to 21.1 IU/ml (14.7-30.2), and the proportion of infants with PT levels ≥10 IU/ml fell from 97% to 67%. Half-life of pertussis-specific IgG in infants in days was 29.4 (95% CI 27.3-31.7) for PT, 29.8 (95% CI 27.7-32.2) for FHA, 31.2 (95% CI 28.9-33.7) for PRN, and 35.8 (95% CI 30.1-44.3) for FIM. CONCLUSION: The half-life of pertussis-specific antibodies in infants induced by maternal Tdap vaccination (29-36 days) is shorter than previously reported. Understanding how the durability of passively-acquired antibodies impacts infant susceptibility to pertussis and response to primary vaccination is critical to refine prevention strategies.

Prevalence and Capsular Types of Group B Streptococci Colonizing Indian Women Living in the United States.

Group B streptococcal rectovaginal colonization prevalence in women of Indian descent living in the United States was 24.7% comparable with US rates but higher than rates reported from India. The capsular polysaccharide types were distinct in that type V was most common and 33% of group B streptococcal strains were nontypeable.

Group B Streptococcal Colonization Among Pregnant Women in Delhi, India.

BACKGROUND: Little is known regarding maternal group B streptococcal (GBS) colonization prevalence and capsular (CPS) serotype distribution among pregnant women in India. The objective of this prospective cohort study was to determine GBS recto-vaginal colonization prevalence in pregnant women at Dr. Ram Manohar Lohia Hospital in Delhi, India. METHODS: Literature review identified reports from India assessing GBS colonization prevalence in pregnant women. Rectal and vaginal swabs were inoculated into Strep B Carrot Broth (Hardy Diagnostics, Santa Maria, CA) and subcultured onto GBS Detect plates (Hardy Diagnostics, Santa Maria, CA). Isolates were serotyped using ImmuLex Strep-B latex kits (Statens Serum Institut, Copenhagen, Denmark). RESULTS: Thirteen studies were identified citing GBS colonization prevalence during pregnancy as 0.47%-16%. Among 300 pregnant women (mean age: 26.9 years; mean gestation: 34 weeks) enrolled (August 2015 to April 2016), GBS colonization prevalence was 15%. Fifteen percent of women had vaginal only, 29% had rectal only and 56% had both sites colonized. CPS types were Ia (13.3%), Ib (4.4%), II (20%), III (22.2%), V (20%) and VII (6.7%); 13.3% were nontypable. Fetal loss in a prior pregnancy at ≥20-weeks gestation was more common in colonized than noncolonized women (15.6% vs. 3.5%; P = 0.004). Employing recent census data for the birth cohort and estimating that 1%-2% of neonates born to colonized women develop early-onset disease, at least 39,000 cases of early-onset disease may occur yearly in India. CONCLUSIONS: Using optimal methods, 15% of third trimester pregnant women in India are GBS colonized. A multivalent vaccine containing 6 CPS types (Ia, Ib, II, III, V and VII) would encompass ~87% of GBS carried by pregnant women in India.

Pertussis serostatus among neonates born to Hispanic women.

The reasons for the higher pertussis incidence among Hispanic infants, compared with among infants of other ethnicities, are unknown. The geometric mean concentration of pertussis toxin-specific immunoglobulin G in serum samples from 220 Hispanic neonates was 8.45 EU/mL, as determined by enzyme-linked immunosorbent assay, and it was significantly lower if mothers were adolescents (4.63 EU/mL; P < or =.001). A lack of maternal immunity is one explanation for pertussis susceptibility in very young Hispanic infants.

Molecular characterization of the first G24P[14] rotavirus strain detected in humans.

Here we report the genome of a novel rotavirus A (RVA) strain detected in a stool sample collected during routine surveillance by the Centers for Disease Control and Prevention's New Vaccine Surveillance Network. The strain, RVA/human-wt/USA/2012741499/2012/G24P[14], has a genomic constellation of G24-P[14]-I2-R2-C2-M2-A3-N2-T9-E2-H3. The VP2, VP3, VP7 and NSP3 genes cluster phylogenetically with bovine strains. The other genes occupy mixed clades containing animal and human strains. Strain RVA/human-wt/USA/2012741499/2012/G24P[14] most likely is the product of interspecies transmission and reassortment events. This is the second report of the G24 genotype and the first report of the G24P[14] genotype combination in humans.

Group B streptococcal colonization and serotype-specific immunity in healthy elderly persons.

BACKGROUND: The burden from group B streptococcal (GBS) disease in elderly persons (age, >or=65 years) has increased. Rates of colonization and prevalence of antibodies against capsular polysaccharides (CPS) that might confer protection against invasive GBS disease in such persons are not defined. METHODS: A cross-sectional survey was conducted in an outpatient setting in Houston. GBS colonization rates in this convenience sample were assessed by self-obtained vaginal and rectal specimens (for women) and rectal and urine specimens (for men). The CPS type distribution among GBS isolates was determined, and CPS-specific antibodies against GBS types Ia, Ib, II, III, and V were quantified by enzyme-linked immunosorbent assays. RESULTS: The GBS colonization rate among 254 healthy elderly participants (mean age, 73 years) was 21.7%. CPS types Ia (22.8%), III (12.3%), and V (47.3%) predominated, and 12.3% of colonizing isolates were nontypeable. Random selection of 1 member of 33 participating married couples did not alter the overall colonization rate (21.7%) or GBS serotype distribution. The geometric mean concentrations of CPS-specific IgG in serum specimens were low and were significantly lower for GBS type V, compared with other serotypes (P<.001). CONCLUSIONS: Adults >or=65 years of age are colonized with GBS at a rate similar to that of younger persons, but older adults are significantly more likely to carry type V, the leading cause of invasive disease in elderly persons, and to lack type V CPS-specific serum IgG. The CPS of type V GBS should be included in candidate GBS vaccines so that adults >or=65 years of age theoretically could be protected against invasive disease.